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Researchers at the University of California, Davis have developed an innovative platform for creating genetically encoded fluorescent biosensors capable of 1) assessing the formation of GPCR homo and heterodimers, and 2) determining how dimerization impacts protomer conformation in response to ligands.The UC Davis IPN has developed a suite of ~24 biosensors based on GPCR dimers.Collectively called, dimerLights, these modular biosensors have the ability to identify novel dimeric drug targets and assess the impact of ligands on their conformations.In addition to the ~24 biosensors that UC Davis has already developed, the modular platform in principle can easily be adapted to enable the discovery and evaluation of broader GPCR homo/heterodimers than have been tested so far.

Researchers at the University of California, Davis have developed a therapy that combines bioactive lipids with antiretroviral drugs to accelerate viral suppression and promote gut mucosal repair in HIV treatment.

Researchers at the University of California, Davis have developed a novel hybrid microbial-derived oxylipin and endocannabinoid-like molecule designed to enhance gut and brain health by improving barrier integrity, reducing inflammation, and providing neuroprotection.

Researchers at the University of California, Davis have developed advanced epigenetic methods and systems that detect and assess developmental risks in embryos caused by maternal stress prior to conception.

Researchers at the University of California, Davis have discovered inhibiting the gene Gc improves metabolic health by protecting against obesity and type 2 diabetes without appetite suppression or muscle loss.

CRISPR-based diagnostic tools can detect DNA or RNA with high sensitivity and specificity. In these systems, enzymes like Cas13a use a guide RNA to find a matching target sequence, which activates the enzyme to cut nearby RNA molecules. This cutting activity is used to generate a fluorescent signal, allowing detection of the target. However, the system can produce background signals even without a target, and it can be difficult to separate signals when testing for multiple targets at once. Improving the ability to distinguish true signals from background noise is a key challenge for making these diagnostics more reliable. This invention comprises a novel method to achieve precise spatio-temporal activity of Cas13a activity using light. Briefly, a single photo-cleavable/photodegradable component that links a canonical cRNA to an interfering DNA segment that suppresses the trans-cleavage activity of Casi3a. Prior to light exposure, activity of Cas13 is inhibitied even in the presence of activating (target) RNA molecules. Upon brief light exposure the Cas13a activity rapidly recovers to the full rate for a given guide-target combination. Several levers exist within this system, specifically the length of interfering DNA segment and the intensity of light, which tune the degree of suppression and the level trans-cleavage activity before and after light exposure, respectively.

In eukaryotic cells, DNA is packaged into chromatin, a dynamic structure that can shift between more open (euchromatin) and condensed (heterochromatin) states to regulate processes like gene expression, DNA repair, and genome organization. This regulation is controlled by chromatin regulators, i.e. proteins that add, remove, or interpret epigenetic modifications, as well as remodel chromatin structure, working alongside transcription factors. These mechanisms are highly conserved across diverse eukaryotic species, underscoring their fundamental biological importance. However, experimentally testing the full function of these proteins remains challenging. Current high-throughput approaches often rely on protein fragments rather than full-length chromatin regulators, which can miss key functional domains and enzymatic activities. Additionally, most chromatin engineering has been developed in a few model systems, creating a need for more versatile tools that can function across a broader range of organisms, including plants and other less-studied eukaryotes. This invention comprises a chromatin regulator protein fused to a DNA-binding protein that in turn modifies gene transcription. The inventors used a multi-kingdom, full length chromatin regulator (CR) library to uncover several potent chromatin regulator proteins. These proteins include the human proteins SAP25, MBD3, RCOR1, MTA2, WDR82, DPY30, the plant proteins CMT3, SWC2, or the yeast proteins CHZ1, IES5, and TTI1 respectively. These proteins are then fused to DNA binding proteins with the product of that fusion being referred to as CR fusion proteins. These CR fusion proteins are then able to proteins to increase or decrease transcription of specific genes in eukaryotic cells when introduced to cells with specific nucleic acids.